[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial precursor

Contribute

Send feedback

Read comments (?) or add your own

Q64536 (PDK2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 107. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial
EC=2.7.11.2

Alternative name(s):
PDK P45
Pyruvate dehydrogenase kinase isoform 2
Short name=PDH kinase 2

Gene names

Name:

Pdk2

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	407 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Serine/threonine kinase that plays a key role in the regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism. Mediates cellular responses to insulin. Plays an important role in maintaining normal blood glucose levels and in metabolic adaptation to nutrient availability. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. Plays a role in the regulation of cell proliferation and in resistance to apoptosis under oxidative stress. Plays a role in p53/TP53-mediated apoptosis. Ref.1 Ref.4 Ref.6 Ref.7 Ref.8
Catalytic activity	ATP + [pyruvate dehydrogenase (acetyl-transferring)] = ADP + [pyruvate dehydrogenase (acetyl-transferring)] phosphate. Ref.1 Ref.3 Ref.4 Ref.7 Ref.8 Ref.10
Enzyme regulation	Activity increases in response to increased acetyl-CoA and NADH levels and upon binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by ADP and pyruvate; these compounds interfere with DLAT binding and thereby inhibit kinase activity. Inhibited by dichloroacetate. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity. Reactive oxygen species cause the formation of disulfide bonds, and thereby inhibit the enzyme. Ref.3 Ref.8
Subunit structure	Homodimer, and heterodimer with PDK1. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). Ref.5 Ref.7 Ref.10
Subcellular location	Mitochondrion matrix Ref.8.
Tissue specificity	Detected in heart (at protein level). Highest level of expression in heart and skeletal muscle and the lowest in spleen and lung. Liver, kidney, brain and testis levels are intermediate. Ref.1 Ref.3 Ref.8
Sequence similarities	Belongs to the PDK/BCKDK protein kinase family. Contains 1 histidine kinase domain.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Glucose metabolism
Cellular component	Mitochondrion
Domain	Transit peptide
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to nutrient Inferred from sequence or structural similarity. Source: UniProtKB glucose homeostasis Inferred from sequence or structural similarity. Source: UniProtKB glucose metabolic process Inferred from electronic annotation. Source: UniProtKB-KW insulin receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-serine phosphorylation Inferred from direct assay Ref.4. Source: UniProtKB regulation of acetyl-CoA biosynthetic process from pyruvate Inferred from sequence or structural similarity. Source: UniProtKB regulation of gluconeogenesis Inferred from sequence or structural similarity. Source: UniProtKB regulation of pH Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	mitochondrial pyruvate dehydrogenase complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from direct assay Ref.7 PubMed 15312755 Ref.3. Source: RGD protein complex binding Inferred from direct assay Ref.7. Source: RGD protein heterodimerization activity Inferred from direct assay Ref.7. Source: RGD protein homodimerization activity Inferred from direct assay Ref.7. Source: RGD protein serine/threonine kinase activity Inferred from direct assay Ref.4. Source: UniProtKB pyruvate dehydrogenase (acetyl-transferring) kinase activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – ?

Mitochondrion Potential

Chain

? – 407

[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial

PRO_0000023442

Regions

Domain

135 – 364

230

Histidine kinase

Nucleotide binding

251 – 258

ATP

Nucleotide binding

309 – 310

ATP

Nucleotide binding

325 – 330

ATP

Sites

Binding site

290

ATP

Secondary structure

407

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

Q64536 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: A01C377290A69EF4
Show »

FASTA

407

46,106

        10         20         30         40         50         60 
MRWFRALLKN ASLAGAPKYI EHFSKFSPSP LSMKQFLDFG SSNACEKTSF TFLRQELPVR 

        70         80         90        100        110        120 
LANIMKEINL LPDRVLSTPS VQLVQSWYVQ SLLDIMEFLD KDPEDHRTLS QFTDALVTIR 

       130        140        150        160        170        180 
NRHNDVVPTM AQGVLEYKDT YGDDPVSNQN IQYFLDRFYL SRISIRMLIN QHTLIFDGST 

       190        200        210        220        230        240 
NPAHPKHIGS IDPNCSVSDV VKDAYDMAKL LCDKYYMASP DLEIQEVNAT NATQPIHMVY 

       250        260        270        280        290        300 
VPSHLYHMLF ELFKNAMRAT VESHESSLTL PPIKIMVALG EEDLSIKMSD RGGGVPLRKI 

       310        320        330        340        350        360 
ERLFSYMYST APTPQPGTGG TPLAGFGYGL PISRLYAKYF QGDLQLFSME GFGTDAVIYL 

       370        380        390        400 
KALSTDSVER LPVYNKSAWR HYQTIQEAGD WCVPSTEPKN TSTYRVS

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of the p45 subunit of pyruvate dehydrogenase kinase." Popov K.M., Kedishvili N.Y., Zhao Y., Gudi R., Harris R.A. J. Biol. Chem. 269:29720-29724(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, TISSUE SPECIFICITY. Tissue: Heart.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Prostate.
[3]	"Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex." Bowker-Kinley M.M., Davis W.I., Wu P., Harris R.A., Popov K.M. Biochem. J. 329:191-196(1998) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, TISSUE SPECIFICITY.
[4]	"Site specificity of four pyruvate dehydrogenase kinase isoenzymes toward the three phosphorylation sites of human pyruvate dehydrogenase." Korotchkina L.G., Patel M.S. J. Biol. Chem. 276:37223-37229(2001) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, FUNCTION.
[5]	"Interaction between the individual isoenzymes of pyruvate dehydrogenase kinase and the inner lipoyl-bearing domain of transacetylase component of pyruvate dehydrogenase complex." Tuganova A., Boulatnikov I., Popov K.M. Biochem. J. 366:129-136(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DLAT.
[6]	"AZD7545, a novel inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2), activates pyruvate dehydrogenase in vivo and improves blood glucose control in obese (fa/fa) Zucker rats." Mayers R.M., Butlin R.J., Kilgour E., Leighton B., Martin D., Myatt J., Orme J.P., Holloway B.R. Biochem. Soc. Trans. 31:1165-1167(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[7]	"Formation of functional heterodimers by isozymes 1 and 2 of pyruvate dehydrogenase kinase." Boulatnikov I., Popov K.M. Biochim. Biophys. Acta 1645:183-192(2003) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, FUNCTION, INTERACTION WITH PDK1, SUBUNIT.
[8]	"Inactivation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species." Hurd T.R., Collins Y., Abakumova I., Chouchani E.T., Baranowski B., Fearnley I.M., Prime T.A., Murphy M.P., James A.M. J. Biol. Chem. 287:35153-35160(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ENZYME REGULATION, TISSUE SPECIFICITY.
[9]	"Structure of pyruvate dehydrogenase kinase. Novel folding pattern for a serine protein kinase." Steussy C.N., Popov K.M., Bowker-Kinley M.M., Sloan R.B. Jr., Harris R.A., Hamilton J.A. J. Biol. Chem. 276:37443-37450(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH ADP.
[10]	"Structural and functional insights into the molecular mechanisms responsible for the regulation of pyruvate dehydrogenase kinase 2." Green T., Grigorian A., Klyuyeva A., Tuganova A., Luo M., Popov K.M. J. Biol. Chem. 283:15789-15798(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH ATP ANALOG AND DLAT, CATALYTIC ACTIVITY, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U10357 mRNA. Translation: AAB54084.1.
BC061823 mRNA. Translation: AAH61823.1.

IPI

IPI00327834.

PIR

A55305.

RefSeq

NP_110499.1. NM_030872.1.

UniGene

Rn.88597.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1JM6	X-ray	2.50	A/B	1-407	[»]
3CRK	X-ray	2.30	A/B	1-407	[»]
3CRL	X-ray	2.61	A/B	1-407	[»]

ProteinModelPortal

Q64536.

SMR

Q64536. Positions 12-404.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q64536. 1 interaction.

STRING

10116.ENSRNOP00000005641.

Proteomic databases

PaxDb

Q64536.

PRIDE

Q64536.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

81530.

KEGG

rno:81530.

UCSC

RGD:69428. rat.

Organism-specific databases

CTD

5164.

RGD

69428. Pdk2.

Phylogenomic databases

eggNOG

COG0642.

HOGENOM

HOG000164315.

HOVERGEN

HBG000511.

InParanoid

Q64536.

K00898.

OrthoDB

EOG4G1MGF.

Gene expression databases

ArrayExpress

Q64536.

Genevestigator

Q64536.

GermOnline

ENSRNOG00000004172. Rattus norvegicus.

Family and domain databases

Gene3D

1.20.140.20. 1 hit.
3.30.565.10. 1 hit.

InterPro

IPR018955. BCDHK/PDK_N.
IPR003594. HATPase_ATP-bd.
IPR005467. Sig_transdc_His_kinase_core.
[Graphical view]

Pfam

PF10436. BCDHK_Adom3. 1 hit.
PF02518. HATPase_c. 1 hit.
[Graphical view]

SMART

SM00387. HATPase_c. 1 hit.
[Graphical view]

SUPFAM

SSF55874. ATP_bd_ATPase. 1 hit.
SSF69012. BCDHK/PDK_N. 1 hit.

PROSITE

PS50109. HIS_KIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q64536.

ChEMBL

CHEMBL3601.

EvolutionaryTrace

Q64536.

NextBio

615077.

Entry information

Entry name

PDK2_RAT

Accession

Primary (citable) accession number: Q64536

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 107 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents